The splicing factor QKI inhibits metastasis by modulating alternative splicing of E-Syt2 in papillary thyroid carcinoma.

Alternative splicing (AS) plays a crucial role in the hallmarks of cancer and can open new avenues for targeted therapies. However, the aberrant AS events and the metastatic cascade in papillary thyroid carcinoma (PTC) remain largely unclear. Here, we identify the splicing factor, quaking protein (QKI), which was significantly downregulated in PTC and correlated with poor survival outcomes in patients with PTC. Functional studies indicated that low expression of QKI promoted the PTC cell growth and metastasis in vitro and in vivo. Mechanistically, low QKI induced exon 14 retention of extended synaptotagmin 2 (E-Syt2) and produced a long isoform transcript (termed E-Syt2L) that acted as an important oncogenic factor of PTC metastasis. Notably, overexpression of long non-coding RNA eosinophil granule ontogeny transcript (EGOT) physically binds to QKI and suppressed its activity by inhibiting ubiquitin specific peptidase 25 (USP25) mediated deubiquitination and subsequent degradation of QKI. Collectively, these data demonstrate the novel mechanistic links between the splicing factor QKI and splicing event in PTC metastasis and support the potential utility of targeting splicing events as a therapeutic strategy for PTC.

Evaluation of a lung cancer screening programme attracting a cohort to actively participate in screening: Honghe Lung Cancer Medical Center Programme.

Background: A lung cancer screening project was conducted by attracting active participation to evaluate its feasibility and effectiveness in areas with poor basic medical education. Methods: This project entailed a prospective, single-arm study which was conducted by means of delivering a lecture on lung cancer at the Honghe Lung Cancer Medical Center to attract public attention and attendance from 28 November 2020 to 21 December 2021. A questionnaire comprising 7 high-risk factors was completed by participants to identify high-risk individuals for further chest low-dose computed tomography examination. Non calcified nodules with a diameter ≥5 mm were deemed positive nodules. The positive nodules were discussed by a multidisciplinary team and treatment suggestions were given. Finally, we analyzed participant information, examination adherence, lung cancer detection rate, and staging. Results: A total of 6,121 individuals were attracted to the project, and 5,925 (96.8%) agreed to participate. Of these, 5,889 (99.4%) completed the survey, with 4,627 (78.6%) in the high-risk group and 1,262 (21.4%) in the non-high-risk group. The proportion of males in the high-risk group was higher than that in the non-high-risk group, and the difference was statistically significant among those aged 40-49 years, 50-59, years and 60-69 years; P<0.01. In the high-risk population, 4,536 (98.0%) of participants adhered to examination, among whom 2,007 (44.2%) with positive nodules, 1,220 (26.9%) with negative nodules, and 1,309 (28.9%) without nodules showed statistical differences in age; P<0.01. The detection rate of lung cancer was 2.2% (99/4,536); 94.0% (93/99) of whom were stage 0-I patients. Conclusions: A health lecture-based approach to improving public participation in regions with poor health education is likely to be effective in promoting the early detection of lung cancer.

Inhibition of activator protein 1 attenuates neuroinflammation and brain injury after experimental intracerebral hemorrhage.

AIMS: Intracerebral hemorrhage (ICH) is a devastating type of stroke without specific treatment. Activator protein 1 (AP-1), as a gene regulator, initiates cytokine expression in response to environmental stimuli. In this study, we investigated the relationship between AP-1 and neuroinflammation-associated brain injury triggered by ICH. METHODS: Intracerebral hemorrhage mice were developed by autologous blood or collagenase infusion. We measured the dynamics of AP-1 in mouse brain tissues during neuroinflammation formation after ICH. The effects of the AP-1 inhibitor SR11302 on brain injury and neuroinflammation as well as the underlying mechanisms were investigated in vivo and in vitro. RESULTS: AP-1 was significantly upregulated in mouse brain tissue as early as 6 hours after ICH, accompanied by elevations in proinflammatory factors, including interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α. Inhibition of AP-1 using SR11302 reduced neurodeficits and brain edema at day 3 after ICH. SR11302 ablated microglial IL-6 and TNF-α production and brain-infiltrating leukocytes in ICH mice. In addition, SR11302 treatment diminished thrombin-induced production of IL-6 and TNF-α in cultured microglia. CONCLUSIONS: Inhibition of AP-1 curbs neuroinflammation and reduces brain injury following ICH.

Limbic encephalitis with relapsing polychondritis: persistent white matter lesions and brain atrophy.

Relapsing polychondritis (RP) is a rare autoimmune disorder affecting cartilage. Limbic encephalitis is a rare central nervous system manifestation of RP. This current case report describes a 66-year-old Chinese male patient who complained of developing myoclonus in the left leg, ataxia and speech difficulties 3 weeks prior to hospital admission. The patient presented with cognitive impairment, sleep disorder and extrapyramidal symptoms. The patient was diagnosed with RP that affected auricular cartilage, which also manifested as limbic encephalitis. Magnetic resonance imaging showed bilateral temporal lobe lesions involving the hippocampi and basal ganglia. Signal abnormalities in the white matter persisted during the 15-month follow-up period after treatment with corticosteroids and intravenous immunoglobulin. Over the same period, the bilateral hippocampi showed significant atrophy.